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Precision Medicine Approach to Alzheimer's Disease: Successful Pilot Project.
Toups, K, Hathaway, A, Gordon, D, Chung, H, Raji, C, Boyd, A, Hill, BD, Hausman-Cohen, S, Attarha, M, Chwa, WJ, et al
Journal of Alzheimer's disease : JAD. 2022;88(4):1411-1421
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Plain language summary
Neurodegenerative diseases such as Alzheimer’s disease are without effective therapeutics. The aim of this study was to compare the effects of a precision medicine approach to historical controls in patients with mild cognitive impairment or early dementia. This study is a proof-of-concept study which recruited twenty-five patients with Alzheimer’s disease or mild cognitive impairment, aged between 50–76 years. Patients were treated for nine months with a personalised, precision medicine protocol that addressed each patient’s identified potentially contributory factors. Results show that a precision medicine approach to the cognitive decline of Alzheimer’s disease and mild cognitive impairment may be an effective strategy, especially with continued optimization over time. Authors conclude that their findings indicate that it is possible to reverse cognitive decline in mild cognitive impairment and early dementia with a personalised, precision medicine (/systems medicine) protocol. This is a small study that requires larger scale initiatives, including examining the practicalities of integrating this approach into healthcare systems.
Abstract
BACKGROUND Effective therapeutics for Alzheimer's disease are needed. However, previous clinical trials have pre-determined a single treatment modality, such as a drug candidate or therapeutic procedure, which may be unrelated to the primary drivers of the neurodegenerative process. Therefore, increasing data set size to include the potential contributors to cognitive decline for each patient, and addressing the identified potential contributors, may represent a more effective strategy. OBJECTIVE To determine whether a precision medicine approach to Alzheimer's disease and mild cognitive impairment is effective enough in a proof-of-concept trial to warrant a larger, randomized, controlled clinical trial. METHODS Twenty-five patients with dementia or mild cognitive impairment, with Montreal Cognitive Assessment (MoCA) scores of 19 or higher, were evaluated for markers of inflammation, chronic infection, dysbiosis, insulin resistance, protein glycation, vascular disease, nocturnal hypoxemia, hormone insufficiency or dysregulation, nutrient deficiency, toxin or toxicant exposure, and other biochemical parameters associated with cognitive decline. Brain magnetic resonance imaging with volumetrics was performed at baseline and study conclusion. Patients were treated for nine months with a personalized, precision medicine protocol, and cognition was assessed at t = 0, 3, 6, and 9 months. RESULTS All outcome measures revealed improvement: statistically significant improvement in MoCA scores, CNS Vital Signs Neurocognitive Index, and Alzheimer's Questionnaire Change score were documented. No serious adverse events were recorded. MRI volumetrics also improved. CONCLUSION Based on the cognitive improvements observed in this study, a larger, randomized, controlled trial of the precision medicine therapeutic approach described herein is warranted.
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Changes in Eating Behaviors of Children with Obesity in Response to Carbohydrate-Modified and Portion-Controlled Diets.
Kirk, S, Woo, JG, Brehm, B, Daniels, SR, Saelens, BE
Childhood obesity (Print). 2017;13(5):377-383
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Paediatric obesity has been shown to be managed most effectively when interventions with multiple components, such as dietary changes, physical activity, supportive parental involvement, and behavioural strategies are included. The aim to the study was to evaluate whether baseline or changes in psychological dimensions of eating behaviours could account for variability in weight status outcomes. For this study, children aged between 7 – 12 years with a fasting blood glucose level of ≤100mg/dl and with a BMI z-score of 1.60 – 2.65 were recruited. The participants were randomly assigned to one of the three diet groups (low carbohydrate, reduced glycaemic load or portion-controlled diet). The study results show that eating behaviours improved significantly with all diets, and increased cognitive restraint and decreased hunger were sustained at 12 months. Disinhibition also remained significantly lower at 12 months for the reduced glycaemic load group. Authors conclude that targeting diets to youth with obesity who have specific characteristics such as sex, race, and/or lower baseline hunger or higher baseline cognitive restraint scores may lead to better outcomes.
Abstract
OBJECTIVE This study's objective was to determine whether two distinct carbohydrate (CHO)-modified diets and a standard portion-controlled (PC) diet differentially impacted children's eating behaviors and whether eating behavior scores predicted lower BMI among children with obesity. METHODS Children (n = 102) aged 7-12 years with obesity were randomly assigned to a 12-month intervention of a low-carbohydrate (LC), reduced glycemic load (RGL), or standard PC diet. The Three-Factor Eating Questionnaire (TFEQ) was completed at baseline, 3, 6, and 12 months by parents to characterize their child's hunger (H), disinhibition (D), and cognitive restraint (CR). Baseline and follow-up TFEQ scores by diet were evaluated relative to BMI status over time. RESULTS All diet groups showed increased CR and decreased H and D from baseline to 3 months, with differences from baseline remaining at 12 months for CR and H. Lower BMI status during study follow-up was associated with different TFEQ scores by diet group (LC and RGL: higher CR; PC: lower H), adjusting for sex, age, and race. Higher CR at follow-up was predicted by race and higher baseline CR; only lower H at baseline predicted lower H at follow-up. CONCLUSION Eating behaviors improved significantly with all diets during the initial 3 months; higher CR and lower H were sustained at treatment's end. BMI outcomes were associated with different eating behaviors in CHO-modified diet groups compared with PC diets. Targeting diets of children with obesity with specific baseline characteristics may lead to improved outcomes.